Preparation of multifunctional nanobubbles and their application in bimodal imaging and targeted combination therapy of early pancreatic cancer

Abstract Pancreatic cancer will gradually become the second leading cause of cancer death due to its poor suitability for surgical treatment, frequent recurrence and metastasis, and insensitivity to radiotherapy and chemotherapy. Strategies for precise early detection and effective targeted treatmen...

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Autores principales:	Hengli Yang, Ping Zhao, Yonggang Zhou, Qiaoying Li, Wenbin Cai, Zongxia Zhao, Jian Shen, Kechun Yao, Yunyou Duan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b35f9948432a4da18cc6ec36388f9661
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spelling	oai:doaj.org-article:b35f9948432a4da18cc6ec36388f96612021-12-02T16:30:24ZPreparation of multifunctional nanobubbles and their application in bimodal imaging and targeted combination therapy of early pancreatic cancer10.1038/s41598-021-82602-92045-2322https://doaj.org/article/b35f9948432a4da18cc6ec36388f96612021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82602-9https://doaj.org/toc/2045-2322Abstract Pancreatic cancer will gradually become the second leading cause of cancer death due to its poor suitability for surgical treatment, frequent recurrence and metastasis, and insensitivity to radiotherapy and chemotherapy. Strategies for precise early detection and effective targeted treatment of pancreatic cancer are urgently needed. Because of its unique advantages, molecular targeted contrast-enhanced ultrasound imaging (CEUI) has generated new opportunities to overcome this challenge. The aim of this study was to explore multifunctional nanobubbles named IR780-NBs-DTX as novel ultrasound contrast agents (UCAs) for dual-mode targeted imaging and photothermal ablation combined with chemotherapy for pancreatic cancer. An optimized “film hydration method” was used to prepare IR780-NBs-DTX in this research. The characteristics and ability of the new UCAs were detected via in vitro, in vivo and ex vivo experiments. The initial dose of 0.15 mg IR-780 iodide/1.0 mg DTX was considered to be the best formula for IR780-NBs-DTX, and the concentration of 6 ×106 bubbles/mL was best for CEUI. The excellent characteristics of IR780-NBs-DTX, including a uniform nanoscale particle size (349.8± 159.1 nm, n= 3), good performance in dual-mode imaging, high stability and reliable biocompatibility, were also proven. In the in vitro cell experiments, IR780-NBs-DTX targeted more pancreatic cancer cells than the control treatments, and the targeting rate was approximately 95.6± 1.7%. Under irradiation with an 808 nm laser, most cells died. Furthermore, the in vivo study demonstrated that IR780-NBs-DTX could precisely detect pancreatic cancer through near infrared fluorescence (NIRF) imaging and CEUI, and the tumor almost disappeared at 18 days after combined treatment. In ex vivo experiments, immunohistochemistry (IHC) and immunofluorescence (IF) showed that the expression of HSP70 increased and that of PCNA decreased, and many apoptotic tumor cells were observed by TUNEL staining in the IR780-NBs-DTX group. The newly prepared IR780-NBs-DTX are novel nanosized UCAs with high efficiency for dual-mode molecular targeted imaging and combined therapy, and they may have future potential applications in the precise detection and effective targeted therapy of small and metastatic lesions in the early stage of pancreatic cancer.Hengli YangPing ZhaoYonggang ZhouQiaoying LiWenbin CaiZongxia ZhaoJian ShenKechun YaoYunyou DuanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-18 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hengli Yang Ping Zhao Yonggang Zhou Qiaoying Li Wenbin Cai Zongxia Zhao Jian Shen Kechun Yao Yunyou Duan Preparation of multifunctional nanobubbles and their application in bimodal imaging and targeted combination therapy of early pancreatic cancer
description	Abstract Pancreatic cancer will gradually become the second leading cause of cancer death due to its poor suitability for surgical treatment, frequent recurrence and metastasis, and insensitivity to radiotherapy and chemotherapy. Strategies for precise early detection and effective targeted treatment of pancreatic cancer are urgently needed. Because of its unique advantages, molecular targeted contrast-enhanced ultrasound imaging (CEUI) has generated new opportunities to overcome this challenge. The aim of this study was to explore multifunctional nanobubbles named IR780-NBs-DTX as novel ultrasound contrast agents (UCAs) for dual-mode targeted imaging and photothermal ablation combined with chemotherapy for pancreatic cancer. An optimized “film hydration method” was used to prepare IR780-NBs-DTX in this research. The characteristics and ability of the new UCAs were detected via in vitro, in vivo and ex vivo experiments. The initial dose of 0.15 mg IR-780 iodide/1.0 mg DTX was considered to be the best formula for IR780-NBs-DTX, and the concentration of 6 ×106 bubbles/mL was best for CEUI. The excellent characteristics of IR780-NBs-DTX, including a uniform nanoscale particle size (349.8± 159.1 nm, n= 3), good performance in dual-mode imaging, high stability and reliable biocompatibility, were also proven. In the in vitro cell experiments, IR780-NBs-DTX targeted more pancreatic cancer cells than the control treatments, and the targeting rate was approximately 95.6± 1.7%. Under irradiation with an 808 nm laser, most cells died. Furthermore, the in vivo study demonstrated that IR780-NBs-DTX could precisely detect pancreatic cancer through near infrared fluorescence (NIRF) imaging and CEUI, and the tumor almost disappeared at 18 days after combined treatment. In ex vivo experiments, immunohistochemistry (IHC) and immunofluorescence (IF) showed that the expression of HSP70 increased and that of PCNA decreased, and many apoptotic tumor cells were observed by TUNEL staining in the IR780-NBs-DTX group. The newly prepared IR780-NBs-DTX are novel nanosized UCAs with high efficiency for dual-mode molecular targeted imaging and combined therapy, and they may have future potential applications in the precise detection and effective targeted therapy of small and metastatic lesions in the early stage of pancreatic cancer.
format	article
author	Hengli Yang Ping Zhao Yonggang Zhou Qiaoying Li Wenbin Cai Zongxia Zhao Jian Shen Kechun Yao Yunyou Duan
author_facet	Hengli Yang Ping Zhao Yonggang Zhou Qiaoying Li Wenbin Cai Zongxia Zhao Jian Shen Kechun Yao Yunyou Duan
author_sort	Hengli Yang
title	Preparation of multifunctional nanobubbles and their application in bimodal imaging and targeted combination therapy of early pancreatic cancer
title_short	Preparation of multifunctional nanobubbles and their application in bimodal imaging and targeted combination therapy of early pancreatic cancer
title_full	Preparation of multifunctional nanobubbles and their application in bimodal imaging and targeted combination therapy of early pancreatic cancer
title_fullStr	Preparation of multifunctional nanobubbles and their application in bimodal imaging and targeted combination therapy of early pancreatic cancer
title_full_unstemmed	Preparation of multifunctional nanobubbles and their application in bimodal imaging and targeted combination therapy of early pancreatic cancer
title_sort	preparation of multifunctional nanobubbles and their application in bimodal imaging and targeted combination therapy of early pancreatic cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b35f9948432a4da18cc6ec36388f9661
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Preparation of multifunctional nanobubbles and their application in bimodal imaging and targeted combination therapy of early pancreatic cancer

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